Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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22868939
TITLE
Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.
ABSTRACT
CONTEXT NlmCategory: BACKGROUND
Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968.
OBJECTIVE NlmCategory: OBJECTIVE
Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking.
DATA SOURCES NlmCategory: METHODS
Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Primary data.
STUDY SELECTION NlmCategory: METHODS
Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Primary data. Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy.
DATA EXTRACTION NlmCategory: METHODS
Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Primary data. Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum.
DATA SYNTHESIS NlmCategory: RESULTS
Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Primary data. Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01).
CONCLUSION NlmCategory: CONCLUSIONS
Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Primary data. Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). These results highlight an increased genetic vulnerability to smoking in early-onset smokers.
DATE PUBLISHED
2012 Aug
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2012/08/08 06:00
pubmed 2012/08/08 06:00
medline 2012/10/19 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Hartz SM Hartz Sarah M SM Washington University School of Medicine, St Louis, Missouri, USA.
Short SE Short Susan E SE
Saccone NL Saccone Nancy L NL
Culverhouse R Culverhouse Robert R
Chen L Chen LiShiun L
Schwantes-An TH Schwantes-An Tae-Hwi TH
Coon H Coon Hilary H
Han Y Han Younghun Y
Stephens SH Stephens Sarah H SH
Sun J Sun Juzhong J
Chen X Chen Xiangning X
Ducci F Ducci Francesca F
Dueker N Dueker Nicole N
Franceschini N Franceschini Nora N
Frank J Frank Josef J
Geller F Geller Frank F
Gubjartsson D Gubjartsson Daniel D
Hansel NN Hansel Nadia N NN
Jiang C Jiang Chenhui C
Keskitalo-Vuokko K Keskitalo-Vuokko Kaisu K
Liu Z Liu Zhen Z
Lyytikäinen LP Lyytikäinen Leo-Pekka LP
Michel M Michel Martha M
Rawal R Rawal Rajesh R
Rosenberger A Rosenberger Albert A
Scheet P Scheet Paul P
Shaffer JR Shaffer John R JR
Teumer A Teumer Alexander A
Thompson JR Thompson John R JR
Vink JM Vink Jacqueline M JM
Vogelzangs N Vogelzangs Nicole N
Wenzlaff AS Wenzlaff Angela S AS
Wheeler W Wheeler William W
Xiao X Xiao Xiangjun X
Yang BZ Yang Bao-Zhu BZ
Aggen SH Aggen Steven H SH
Balmforth AJ Balmforth Anthony J AJ
Baumeister SE Baumeister Sebastian E SE
Beaty T Beaty Terri T
Bennett S Bennett Siiri S
Bergen AW Bergen Andrew W AW
Boyd HA Boyd Heather A HA
Broms U Broms Ulla U
Campbell H Campbell Harry H
Chatterjee N Chatterjee Nilanjan N
Chen J Chen Jingchun J
Cheng YC Cheng Yu-Ching YC
Cichon S Cichon Sven S
Couper D Couper David D
Cucca F Cucca Francesco F
Dick DM Dick Danielle M DM
Foroud T Foroud Tatiana T
Furberg H Furberg Helena H
Giegling I Giegling Ina I
Gu F Gu Fangyi F
Hall AS Hall Alistair S AS
Hällfors J Hällfors Jenni J
Han S Han Shizhong S
Hartmann AM Hartmann Annette M AM
Hayward C Hayward Caroline C
Heikkilä K Heikkilä Kauko K
Hewitt JK Hewitt John K JK
Hottenga JJ Hottenga Jouke Jan JJ
Jensen MK Jensen Majken K MK
Jousilahti P Jousilahti Pekka P
Kaakinen M Kaakinen Marika M
Kittner SJ Kittner Steven J SJ
Konte B Konte Bettina B
Korhonen T Korhonen Tellervo T
Landi MT Landi Maria-Teresa MT
Laatikainen T Laatikainen Tiina T
Leppert M Leppert Mark M
Levy SM Levy Steven M SM
Mathias RA Mathias Rasika A RA
McNeil DW McNeil Daniel W DW
Medland SE Medland Sarah E SE
Montgomery GW Montgomery Grant W GW
Muley T Muley Thomas T
Murray T Murray Tanda T
Nauck M Nauck Matthias M
North K North Kari K
Pergadia M Pergadia Michele M
Polasek O Polasek Ozren O
Ramos EM Ramos Erin M EM
Ripatti S Ripatti Samuli S
Risch A Risch Angela A
Ruczinski I Ruczinski Ingo I
Rudan I Rudan Igor I
Salomaa V Salomaa Veikko V
Schlessinger D Schlessinger David D
Styrkársdóttir U Styrkársdóttir Unnur U
Terracciano A Terracciano Antonio A
Uda M Uda Manuela M
Willemsen G Willemsen Gonneke G
Wu X Wu Xifeng X
Abecasis G Abecasis Goncalo G
Barnes K Barnes Kathleen K
Bickeböller H Bickeböller Heike H
Boerwinkle E Boerwinkle Eric E
Boomsma DI Boomsma Dorret I DI
Caporaso N Caporaso Neil N
Duan J Duan Jubao J
Edenberg HJ Edenberg Howard J HJ
Francks C Francks Clyde C
Gejman PV Gejman Pablo V PV
Gelernter J Gelernter Joel J
Grabe HJ Grabe Hans Jörgen HJ
Hops H Hops Hyman H
Jarvelin MR Jarvelin Marjo-Riitta MR
Viikari J Viikari Jorma J
Kähönen M Kähönen Mika M
Kendler KS Kendler Kenneth S KS
Lehtimäki T Lehtimäki Terho T
Levinson DF Levinson Douglas F DF
Marazita ML Marazita Mary L ML
Marchini J Marchini Jonathan J
Melbye M Melbye Mads M
Mitchell BD Mitchell Braxton D BD
Murray JC Murray Jeffrey C JC
Nöthen MM Nöthen Markus M MM
Penninx BW Penninx Brenda W BW
Raitakari O Raitakari Olli O
Rietschel M Rietschel Marcella M
Rujescu D Rujescu Dan D
Samani NJ Samani Nilesh J NJ
Sanders AR Sanders Alan R AR
Schwartz AG Schwartz Ann G AG
Shete S Shete Sanjay S
Shi J Shi Jianxin J
Spitz M Spitz Margaret M
Stefansson K Stefansson Kari K
Swan GE Swan Gary E GE
Thorgeirsson T Thorgeirsson Thorgeir T
Völzke H Völzke Henry H
Wei Q Wei Qingyi Q
Wichmann HE Wichmann H-Erich HE
Amos CI Amos Christopher I CI
Breslau N Breslau Naomi N
Cannon DS Cannon Dale S DS
Ehringer M Ehringer Marissa M
Grucza R Grucza Richard R
Hatsukami D Hatsukami Dorothy D
Heath A Heath Andrew A
Johnson EO Johnson Eric O EO
Kaprio J Kaprio Jaakko J
Madden P Madden Pamela P
Martin NG Martin Nicholas G NG
Stevens VL Stevens Victoria L VL
Stitzel JA Stitzel Jerry A JA
Weiss RB Weiss Robert B RB
Kraft P Kraft Peter P
Bierut LJ Bierut Laura J LJ
INVESTIGATORS
JOURNAL
VOLUME: 69
ISSUE: 8
TITLE: Archives of general psychiatry
ISOABBREVIATION: Arch Gen Psychiatry
YEAR: 2012
MONTH: Aug
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1538-3636
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Arch Gen Psychiatry
COUNTRY: United States
ISSNLINKING: 0003-990X
NLMUNIQUEID: 0372435
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adolescent Development drug effects
Adult drug effects
Age of Onset drug effects
Europe epidemiology
Female epidemiology
Gene-Environment Interaction epidemiology
Genetic Association Studies epidemiology
Genetic Predisposition to Disease epidemiology
Humans epidemiology
Male epidemiology
Nerve Tissue Proteins genetics
Nicotine pharmacology
Polymorphism, Single Nucleotide pharmacology
Receptors, Nicotinic genetics
Severity of Illness Index genetics
Smoking genetics
Tobacco Use Disorder psychology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CHRNA5 protein, human
0 Nerve Tissue Proteins
0 Receptors, Nicotinic
6M3C89ZY6R Nicotine
OTHER ID's
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